A5061504579- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Advanced Fluorescence Microscopy Techniques
- RNA regulation and disease
- RNA Research and Splicing
- Nuclear Structure and Function
- Biotin and Related Studies
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Spatial Neglect and Hemispheric Dysfunction
- Neuroscience and Neural Engineering
- Hemodynamic Monitoring and Therapy
- Neurobiology of Language and Bilingualism
- Stroke Rehabilitation and Recovery
- Cardiac, Anesthesia and Surgical Outcomes
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neuroendocrine Tumor Research Advances
- Pulmonary Hypertension Research and Treatments
University of Trento
2017-2023
IRCCS Istituto Auxologico Italiano
2023
Istituti di Ricovero e Cura a Carattere Scientifico
2023
University of Milano-Bicocca
2022
Dulbecco Telethon Institute
2017-2021
Azienda Ospedaliera Sant'Andrea
2018
Sapienza University of Rome
2018
University of Milan
2015-2016
Neuroscience Institute
2014
National Research Council
2014
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including predicted C-terminal WD40 repeats. In this study, we analyzed functional molecular features conferred by domain. Electron microscopic analysis purified domain revealed doughnut-shaped particles, providing experimental evidence for its fold. We demonstrate binds sequesters synaptic vesicles via...
Abstract The Excitatory Amino Acid Transporter 2 (EAAT2) accounts for 80% of brain glutamate clearance and is mainly expressed in astrocytic perisynaptic processes. EAAT2 function finely regulated by endocytic events, recycling to the plasma membrane degradation. Noteworthy, deficits have been associated with neuronal excitotoxicity neurodegeneration. In this study, we show that trafficking impaired leucine-rich repeat kinase (LRRK2) pathogenic variant G2019S, a common cause late-onset...
Autism spectrum disorders are neurodevelopmental conditions with diverse aetiologies, all characterized by common core symptoms such as impaired social skills and communication, well repetitive behaviour. Cell adhesion molecules, receptor tyrosine kinases associated downstream signalling have been strongly implicated in both neurodevelopment autism disorders. We found that downregulation of the cell molecule NEGR1 or kinase fibroblast growth factor 2 (FGFR2) similarly affects neuronal...
A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth subsequent morphological functional development neuronal processes. In order to gain a more detailed description these events at molecular level, we have developed cell surface biotinylation assay isolate, detect, quantify membrane proteins. When applied our investigate neuron maturation in vitro, identified 439 differentially expressed proteins, including 20 members immunoglobulin...
Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson's disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed features attributed to by C-terminal domains. We combined TIRF microscopy synaptopHluorin assay visualize synaptic vesicle trafficking. found that have opposite impact on dynamics. Biochemical analysis demonstrated different proteins...
IgLON proteins are GPI anchored adhesion molecules that control neurite outgrowth. In particular, Negr1 down-regulation negatively influences neuronal arborization in vitro and vivo. the present study, we found metalloprotease ADAM10 releases from membrane. Ectodomain shedding several mechanisms, including survival, synaptogenesis formation of trees. By combining morphological analysis virus-mediated selective protein silencing primary murine cortical neurons, pharmacologically inhibition...
Abstract The Parkinson’s disease (PD)-associated kinase Leucine-Rich Repeat Kinase 2 (LRRK2) is a crucial modulator of the autophagy-lysosome pathway, but unclarity exists on precise mechanics its role and direction this modulation. In particular, LRRK2 involved in degradation pathological alpha-synuclein, with pathogenic mutations precipitating neuropathology cellular animal models PD, significant proportion patients presenting Lewy neuropathology. Defects autophagic processing lysosomal...
Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease. LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed functional molecular consequences novel variant, E193K, identified an Italian family. E193K substitution does not influence activity. Instead it affects biochemical properties, such as phosphorylation Ser935 affinity for...
Primary neuronal culture from rodents is a well-established model to investigate cellular neurobiology in vitro. However, for this purpose cell cultures need be generated expressly, requiring extensive animal handling. Furthermore, often the preparation of fresh generates an excess cells that are ultimately wasted. Therefore ability successfully cryopreserve primary neural would represent important resource neuroscience research and allow significantly reduce sacrifice animals. We describe...
Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain scaffolding protein with and GTPase activities involved in synaptic vesicle (SV) dynamics. While its role Parkinson's disease has been largely investigated, little known about LRRK2 physiological until now few proteins have described as substrates. We previously demonstrated that through WD40 domain interacts synapsin I, an important SV-associated phosphoprotein neuronal development the regulation of neurotransmitter release. To...
Abstract Parkinson’s disease is characterized by the progressive degeneration of dopaminergic neurons within substantia nigra pars compacta and presence protein aggregates in surviving neurons. The LRRK2 G2019S mutation one major determinants familial cases leads to late-onset with pleomorphic pathology, including α-synuclein accumulation deposition inclusions. We demonstrated that phosphorylates N-ethylmaleimide sensitive factor (NSF). observed containing NSF basal ganglia specimens from...
The Negr1 gene has been significantly associated with major depression in genetic studies. encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate expression of genes belonging to Negr1-Fgfr2 pathway Flinders sensitive line (FSL) rats, corticosterone-treated mouse model depression, primary neurons. Adam10 were mostly affected antidepressant treatment, opposite...
Neuroblastoma is among the most common childhood cancers. in advanced stages one of intractable pediatric cancers, notwithstanding recent therapeutic advances. ALK mutations are leading cause hereditary neuroblastoma and account for more than 14% somatically acquired alterations. kinase activity currently main targets pharmacological strategies. However, evidence from fusion-positive lung cancer studies has shown that resistance to inhibition arises during therapy, causing a relapse within...
Mutations in the PRKN gene (encoding parkin) have been linked to most frequent known cause of recessive Parkinson’s disease (PD), and parkin dysfunction represents a risk factor for sporadic PD. Parkin is widely neuroprotective through different cellular pathways, as it protects dopaminergic neurons from apoptosis series animal models The mitochondrial protein apoptosis-inducing (AIF) an important cell death effector, which, upon stress many paradigms, redistributed mitochondria nucleus...
Abstract The LRRK2 protein consists of multiple functional domains, including protein-binding domains at its N and C-terminus. Mutations in the Leucine-rich repeat kinase 2 gene ( ) have been linked to familial sporadic Parkinson’s disease (PD). We recently described a novel variant falling within N-terminal armadillo repeats, E193K. Herein, our aim is investigate impact domain E193K on vesicle trafficking. By combining Total Internal Reflection Fluorescence (TIRF) microscopy synaptopHluorin...
Nup358 (also known as RanBP2) is a member of the large nucleoporin family that constitutes nuclear pore complex. Depending on cell type and physiological state, interacts with specific partner proteins influences distinct mechanisms independent its role in nucleocytoplasmic transport. Here, we provide evidence associates selectively axon initial segment (AIS) mature neurons, mediated by AIS scaffold protein ankyrin-G (AnkG, also Ank3). The N-terminus demonstrated to be sufficient for...
The application of single-cell RNA sequencing (scRNASeq) represents a unique approach to identify hundreds millions cells in mammalian cortical multilayers at different stages embryogenesis. ScRNASeq technology applied neurological studies requires the use fresh starting materials because standard cryopreservation methods do not guarantee high viability primary derived from dissected brain areas.Here we set up and validate an innovative strategy perform scRNASeq cryopreserved isolated E15.5...
Abstract The Parkinson’s disease (PD)-associated kinase Leucine-Rich Repeat Kinase 2 (LRRK2) is a potent modulator of autophagy and impacts on lysosome biology function, but unclarity exists the precise mechanics its role direction this modulation. LRRK2 also involved in degradation pathological alpha-synuclein, with pathogenic mutations precipitating neuropathology cellular animal models PD, most familial cases manifesting Lewy neuropathology. Defects autophagic processing lysosomal...
SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation these targets.The 3'-UTRs brain compared to other tissues predict important roles for miRNAs.Supporting this notion, we found miRNAs co-evolved their target transcripts, non-coding pseudogenes miRNA recognition elements...
Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans envelope of a cell and provides channel through which RNA move between nucleus cytoplasm vice versa. NUP disruptions have great impact on pathophysiology neurodegenerative diseases (NDDs). Although downregulation Nup358 leads to reduction in scaffold protein ankyrin-G at axon initial segment (AIS) mature neurons, function neurons remains elusive. To investigate whether plays any role neuronal...
Primary neuronal culture from rodents is a key tool in neurobiology.However, the preparation of primary cultures requires precise planning, starting animal mating.Furthermore, each generates high amount cells that eventually go wasted.The possibility to cryopreserve neural represents resource for vitro studies and significantly reduces sacrifice animals.Here we describe Neurostore buffer supports cryopreservation neurons.
Abstract The Excitatory Amino Acid Transporter 2 (EAAT2) accounts for 80 % of brain glutamate clearance and is mainly expressed in astrocytic perisynaptic processes. EAAT2 function finely regulated by endocytic events, recycling to the plasma membrane degradation. Noteworthy, deficits have been associated with neuronal excitotoxicity neurodegeneration. In this study, we show that trafficking impaired leucine-rich repeat kinase (LRRK2) pathogenic variant G2019S, a common cause late-onset...